Ongoing RAMP 203 Trial Assessing a More
Complete Vertical Blockade with RAF/MEK and KRAS G12C Inhibition
Along RAS Pathway to Improve Outcomes in KRAS G12C-Mutant NSCLC
Confirmed Responses Observed in Both KRAS G12C
Inhibitor Naïve and Pre-treated Patients in Initial RAMP 203 Trial
Results; Enrollment Ongoing in Expansion Phase
Verastem Oncology (Nasdaq:VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today announced the U.S. Food and Drug Administration (FDA) has
granted Fast Track Designation to Verastem Oncology’s
investigational RAF/MEK clamp, avutometinib, in combination with
Amgen’s KRAS G12C inhibitor, LUMAKRASTM (sotorasib), for the
treatment of patients with KRAS G12C-mutant metastatic non-small
cell lung cancer (NSCLC) who have received at least one prior
systemic therapy and have not been previously treated with a KRAS
G12C inhibitor. Fast Track is a process designed to facilitate the
development and expedite the review of new drugs intended to treat
or prevent serious conditions and address unmet medical need.
“Receiving Fast Track Designation for the combination of
avutometinib and sotorasib reinforces the importance of improving
the depth of MAPK pathway inhibition to enhance tumor regression
relative to KRAS G12C inhibition alone and the potential of the
combination of avutometinib and sotorasib in KRAS G12C mutant
locally advanced or metastatic NSCLC,” said Dan Paterson, President
and CEO, Verastem Oncology. “Given that KRAS G12C is the most
common KRAS mutation in NSCLC, the advancement of the combination
is important in understanding potential new treatment approaches.
We look forward to continued interaction with the FDA as we advance
the development of this promising treatment regimen.”
While newer targeted therapies specific to KRAS G12C-mutant
NSCLC have shown significant promise, avutometinib targets the RAS
pathway, which is a common source of acquired mutation. Preclinical
proof-of-concept studies demonstrated improvements with the
combination of avutometinib and sotorasib vs sotorasib alone,
including deeper tumor regression through enhanced blockade of ERK
activation and a decrease in the frequency of relapse of tumors.
The RAMP 203 clinical development program will determine whether
the promising preclinical results observed with the combination of
avutometinib with sotorasib translate into improved clinical
outcomes for patients with KRAS G12C-mutant locally advanced or
metastatic NSCLC who have received prior therapy for metastatic
disease and have not been previously treated with a KRAS G12C
inhibitor.
Initial results of the RAMP 203 (NCT05074810) Phase 1/2,
multicenter, open label, dose evaluation/expansion study evaluating
the efficacy and safety of avutometinib + sotorasib in patients
with KRAS G12C-mutant NSCLC who have not been previously treated
with a KRAS G12C inhibitor as well as in patients who have been
previously treated with a KRAS G12C inhibitor demonstrated
confirmed responses in both KRAS G12C inhibitor resistant and naïve
patients. The pharmacokinetic profile of avutometinib in
combination with sotorasib in the RAMP 203 trial was similar to
results in monotherapy studies. No drug-drug interactions were
observed between avutometinib and sotorasib. Avutometinib 4.0 mg PO
BIW 21/28 days + sotorasib 960 mg PO QD 28/28 days was selected as
RP2D based on dose limiting toxicity (DLT) assessment. These
initial RAMP 203 results were presented at the AACR-NCI-EORTC
International Conference on Molecular Targets and Cancer
Therapeutics in October, 2023. Enrollment of patients with KRAS
G12C-mutant NSCLC who are either naïve to or previously treated
with a KRAS G12C inhibitor is ongoing in the expansion phase of
RAMP 203 with updated results expected in the first half of
2024.
About Avutometinib
Avutometinib is a RAF/MEK clamp that induces inactive complexes
of MEK with ARAF, BRAF and CRAF potentially creating a more
complete and durable anti-tumor response through maximal RAS
pathway inhibition. Avutometinib is currently in late-stage
development.
In contrast to currently available MEK inhibitors, avutometinib
blocks both MEK kinase activity and the ability of RAF to
phosphorylate MEK. This unique mechanism allows avutometinib to
block MEK signaling without the compensatory activation of MEK that
appears to limit the efficacy of other inhibitors. The U.S. Food
and Drug Administration granted Breakthrough Therapy designation
for the combination of Verastem Oncology’s investigational RAF/MEK
clamp avutometinib, with defactinib, its FAK inhibitor, for the
treatment of all patients with recurrent low-grade serous ovarian
cancer (LGSOC) regardless of KRAS status after one or more prior
lines of therapy, including platinum-based chemotherapy.
Verastem Oncology is currently conducting clinical trials with
its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part
of its RAMP (Raf And Mek Program)
trials. RAMP 201 is a Phase 2 registration-directed trial of
avutometinib in combination with defactinib in patients with
recurrent LGSOC and has completed enrollment in the dose
optimization and expansion phases and is enrolling for low-dose
evaluation. Verastem Oncology has established clinical
collaborations with Amgen and Mirati to evaluate LUMAKRAS™
(sotorasib) and KRAZATI™ (adagrasib) in combination with
avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 and
RAMP 204 trials, respectively. Supported by the “Therapeutic
Accelerator Award” Verastem Oncology received from PanCAN, the
Company is conducting RAMP 205, a Phase 1b/2 clinical trial
evaluating avutometinib and defactinib with
gemcitabine/nab-paclitaxel in patients with front-line metastatic
pancreatic cancer.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a development-stage
biopharmaceutical company committed to the development and
commercialization of new medicines to improve the lives of patients
diagnosed with cancer. Our pipeline is focused on novel small
molecule drugs that inhibit critical signaling pathways in cancer
that promote cancer cell survival and tumor growth, including
RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition. For
more information, please visit www.verastem.com.
Forward-Looking Statements Notice
This press release includes forward-looking statements about
Verastem Oncology’s strategy, future plans and prospects, including
statements related to the expected outcome and benefits of the
collaboration with Genfleet, the potential clinical value of
various of its clinical trials, the timing of commencing and
completing trials, including topline data reports, interactions
with regulators and potential for additional development programs
involving Verastem Oncology’s lead compound. The words
"anticipate," "believe," "estimate," "expect," "intend," "may,"
"plan," "predict," "project," "target," "potential," "will,"
"would," "could," "should," "continue," “can,” “promising” and
similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. Each forward-looking statement is subject
to risks and uncertainties that could cause actual results to
differ materially from those expressed or implied in such
statement.
Applicable risks and uncertainties include the risks and
uncertainties, among other things, regarding: the success in the
development and potential commercialization of our product
candidates, including avutometinib in combination with other
compounds, including defactinib, LUMAKRASTM and others; the
uncertainties inherent in research and development, such as
negative or unexpected results of clinical trials, the occurrence
or timing of applications for our product candidates that may be
filed with regulatory authorities in any jurisdictions; whether and
when regulatory authorities in any jurisdictions may approve any
such applications that may be filed for our product candidates,
and, if approved, whether our product candidates will be
commercially successful in such jurisdictions; our ability to
obtain, maintain and enforce patent and other intellectual property
protection for our product candidates; the scope, timing, and
outcome of any legal proceedings; decisions by regulatory
authorities regarding trial design, labeling and other matters that
could affect the timing, availability or commercial potential of
our product candidates; whether preclinical testing of our product
candidates and preliminary or interim data from clinical trials
will be predictive of the results or success of ongoing or later
clinical trials; that the timing, scope and rate of reimbursement
for our product candidates is uncertain; that third-party payors
(including government agencies) may not reimburse; that there may
be competitive developments affecting our product candidates; that
data may not be available when expected; that enrollment of
clinical trials may take longer than expected; that our product
candidates will cause adverse safety events and/or unexpected
concerns may arise from additional data or analysis, or result in
unmanageable safety profiles as compared to their levels of
efficacy; that our product candidates may experience manufacturing
or supply interruptions or failures; that any of our third party
contract research organizations, contract manufacturing
organizations, clinical sites, or contractors, among others, who we
rely on fail to fully perform; that we face substantial
competition, which may result in others developing or
commercializing products before or more successfully than we do
which could result in reduced market share or market potential for
our product candidates; that we will be unable to successfully
initiate or complete the clinical development and eventual
commercialization of our product candidates; that the development
and commercialization of our product candidates will take longer or
cost more than planned, including as a result of conducting
additional studies; that we may not have sufficient cash to fund
our contemplated operations; that we may not attract and retain
high quality personnel; that we or Chugai Pharmaceutical Co., Ltd.
will fail to fully perform under the avutometinib license
agreement; that our target market for our product candidates might
be smaller than we are presently estimating; that Secura Bio, Inc.
will fail to fully perform under the asset purchase agreement with
Secura Bio, Inc., including in relation to milestone payments; that
we will not see a return on investment on the payments we have and
may continue to make pursuant to the collaboration and option
agreement with Genfleet or that Genfleet will fail to fully perform
under the agreement; that we may be unable to obtain adequate
financing in the future through product licensing, co-promotional
arrangements, public or private equity, debt financing or
otherwise; that we will not pursue or submit regulatory filings for
our product candidates; and that our product candidates will not
receive regulatory approval, become commercially successful
products, or result in new treatment options being offered to
patients.
Other risks and uncertainties include those identified under the
heading “Risk Factors” in the Company’s Annual Report on Form 10-K
for the year ended December 31, 2022 as filed with the Securities
and Exchange Commission (SEC) on March 14, 2023 and in any
subsequent filings with the SEC. The forward-looking statements
contained in this press release reflect Verastem Oncology’s views
as of the date hereof, and the Company does not assume and
specifically disclaims any obligation to update any forward-looking
statements whether as a result of new information, future events or
otherwise, except as required by law.
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version on businesswire.com: https://www.businesswire.com/news/home/20240118664635/en/
Investors: Ryan Porter Argot Partners +1 212-600-1902
ryan.porter@argotpartners.com
Media: Lisa Buffington Corporate Communications +1
781-292-4502 lbuffington@verastem.com
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